Circulating endocannabinoidome signatures of disease activity in amyotrophic lateral sclerosis.
Bibliographic record
Abstract
Abstract Objectives Preclinical studies of amyotrophic lateral sclerosis (ALS) have shown altered endocannabinoid (eCB) signalling that may contribute to the disease. Results from human studies are sparse and inconclusive. The aim of this study was to determine the association between serum levels of eCBs or their congeners, the so-called endocannabinoidome, and disease status and activity in ALS patients. Methods Serum concentrations of the eCBs 2-arachidonoylglycerol (2AG) and N-arachidonoylethanolamine (AEA), and AEA congeners, palmitoylethanolamide (PEA), oleoylethanolamide (OEA), eicosapentaenoylethanolamide (EPEA), 2-docosahexaenoylglycerol (2-DHG) and docosahexaenoylethanolamide (DHEA) were measured in samples from 65 ALS patients, 32 healthy controls (HC) and 16 neurological disease controls (NALS). A subset of 46 ALS patients underwent a longitudinal study. Disease activity and progression were correlated with eCB and congener levels. Results Most circulating mediators were higher in ALS than HC (all p < 0.001), but not NALS. Across clinical stages, ALS patients showed increased levels of PEA, OEA, and EPEA (all p < 0.02), which were confirmed by the longitudinal study (all p < 0.03). Serum PEA and OEA levels were independent predictors of survival and OEA levels were higher in patients complaining of appetite loss. Cluster analysis revealed two distinct profiles of circulating mediators associated with corresponding patterns of disease activity (severe vs. mild). Patients belonging to the “severe” cluster showed significantly higher levels of OEA, PEA and lower levels of 2-DHG compared to NALS and HC. Interpretation Circulating endocannabinoidome profiles are indicative of disease activity, thus possibly paving the way to personalised, rather than a “one-fit-all”, therapeutic approaches targeting the endocannabinoidome.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".